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Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer

Martey, Orleans ; Nimick, Mhairi ; Taurin, Sebastien ; Sundararajan, Vignesh ; Greish, Khaled ; Rosengren, Rhonda J

International journal of nanomedicine, 2017-01, Vol.12, p.7225-7237 [Periódico revisado por pares]

New Zealand: Dove Medical Press Limited

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Título:
Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer
Autor: Martey, Orleans ; Nimick, Mhairi ; Taurin, Sebastien ; Sundararajan, Vignesh ; Greish, Khaled ; Rosengren, Rhonda J
Assuntos: Animals ; Apoptosis ; Apoptosis - drug effects ; Bioavailability ; biodistribution ; Breast cancer ; Cancer therapies ; Cell cycle ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Chemotherapy ; Comparative analysis ; Curcumin - analogs & derivatives ; Curcumin - pharmacology ; Curcumin - therapeutic use ; Curcumin - toxicity ; curcumin derivatives ; Cytotoxicity ; Disease Models, Animal ; EGFR ; Female ; Growth ; Health aspects ; Humans ; Kinases ; Laboratories ; Lung cancer ; Maleates - chemistry ; Mice, Inbred BALB C ; Mice, SCID ; Micelles ; nanomedicine ; Nanoparticles ; Neoplasm Proteins - metabolism ; Original Research ; Permeability ; Prognosis ; Proteins ; Styrene - chemistry ; Tissue Distribution - drug effects ; Triple Negative Breast Neoplasms - drug therapy ; Triple Negative Breast Neoplasms - pathology ; Womens health ; Xenograft Model Antitumor Assays
É parte de: International journal of nanomedicine, 2017-01, Vol.12, p.7225-7237
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Patients with triple negative breast cancer have a poor prognosis due in part to the lack of targeted therapies. In the search for novel drugs, our laboratory has developed a second-generation curcumin derivative, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidine-4-one (RL71), that exhibits potent in vitro cytotoxicity. To improve the clinical potential of this drug, we have encapsulated it in styrene maleic acid (SMA) micelles. SMA-RL71 showed improved biodistribution, and drug accumulation in the tumor increased 16-fold compared to control. SMA-RL71 (10 mg/kg, intravenously, two times a week for 2 weeks) also significantly suppressed tumor growth compared to control in a xenograft model of triple negative breast cancer. Free RL71 was unable to alter tumor growth. Tumors from SMA-RL71-treated mice showed a decrease in angiogenesis and an increase in apoptosis. The drug treatment also modulated various cell signaling proteins including the epidermal growth factor receptor, with the mechanisms for tumor suppression consistent with previous work with RL71 in vitro. The nanoformulation was also nontoxic as shown by normal levels of plasma markers for liver and kidney injury following weekly administration of SMA-RL71 (10 mg/kg) for 90 days. Thus, we report clinical potential following encapsulation of a novel curcumin derivative, RL71, in SMA micelles.
Editor: New Zealand: Dove Medical Press Limited
Idioma: Inglês

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Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer

Martey, Orleans ; Nimick, Mhairi ; Taurin, Sebastien ; Sundararajan, Vignesh ; Greish, Khaled ; Rosengren, Rhonda J

New Zealand: Dove Medical Press Limited

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